The contribution of periaqueductal gray in the regulation of physiological and pathological behaviors

Abstract

Periaqueductal gray (PAG), an integration center for neuronal signals, is located in the midbrain and regulates multiple physiological and pathological behaviors, including pain, defensive and aggressive behaviors, anxiety and depression, cardiovascular response, respiration, and sleep-wake behaviors. Due to the different neuroanatomical connections and functional characteristics of the four functional columns of PAG, different subregions of PAG synergistically regulate various instinctual behaviors. In the current review, we summarized the role and possible neurobiological mechanism of different subregions of PAG in the regulation of pain, defensive and aggressive behaviors, anxiety, and depression from the perspective of the up-down neuronal circuits of PAG. Furthermore, we proposed the potential clinical applications of PAG. Knowledge of these aspects will give us a better understanding of the key role of PAG in physiological and pathological behaviors and provide directions for future clinical treatments.

Keywords: defensive behavior; pain modulation; periaqueductal gray; predatory hunting; sleep-wake states.

FIGURE 1

Input and output of neuronal circuits in different subregions of PAG. Au1, primary auditory cortex; AHN, anterior hypothalamic area; BST, bed nucleus of the stria terminalis; CeA, central amygdala; CnF, cuneiform nucleus; DMPAG, dorsomedial periaqueductal gray; DLPAG, dorsolateral periaqueductal gray; LPAG, lateral periaqueductal gray; MPA, medial preoptic area; mPFC, medial prefrontal cortex; M1, primary motor cortex; NPH, nucleus praepositus hypoglossi; NTS, nucleus tractus solitarius; PMD, dorsal premammillary nucleus; PB, parabrachial complex; PBG, periparabigeminal nucleus; RVLM, rostral ventrolateral medulla; RAmb, retroambiguus nucleus; SC, superior colliculus; Sp5, spinal trigeminal nucleus; VLPAG, ventrolateral periaqueductal gray; VLM, ventrolateral medulla; V2, secondary visual cortex; VRG, ventral respiratory group.